title: Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers - prehaptens and prohaptens.
abstract: Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety.
authors.affiliation: Division of Dermatochemistry and Skin Allergy, Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96, Gothenburg, Sweden.
authors.forename: Ann-Therese
authors.initials: AT
authors.lastname: Karlberg
authors.forename: Anna
authors.initials: A
authors.lastname: Börje
authors.forename: Jeanne
authors.initials: J
authors.lastname: Duus Johansen
authors.forename: Carola
authors.initials: C
authors.lastname: Lidén
authors.forename: Suresh
authors.initials: S
authors.lastname: Rastogi
authors.forename: David
authors.initials: D
authors.lastname: Roberts
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Uter
authors.forename: Ian R
authors.initials: IR
authors.lastname: White
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D009822:Oils, Volatile / Q000009:adverse effects / Q000737:chemistry; D010476:Perfume / Q000009:adverse effects* / Q000737:chemistry
chemical_list: D000485:Allergens; D006241:Haptens; D009822:Oils, Volatile; D010476:Perfume
keywords: SCCS; abiotic and biotic activation; autoxidation; directive 76/768/ECC; fragrance allergens; prehaptens; prohaptens; scientific opinion